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People who often browse the news may have this feeling: There are reports of rare diseases all day long, why are rare diseases so rare?
The so-called rare diseases are very rare diseases. The types of diseases vary from country to country, and the criteria for defining rare diseases are also different. In Europe, if the incidence rate is less than 1/2000, it can be called a rare disease; in the United States, it is classified according to the number of cases. If the total number of patients with a disease is less than 200,000, it is considered a rare disease; in my country, Beijing The medical society defines rare diseases as diseases with a prevalence rate between 0.1‰ and 0.65‰. [1]
0.1‰ is 1 in 10,000. It seems that there is no need to worry at all. However, due to the huge population base in my country, rare diseases are not particularly rare.
Secretory breast cancer
According to media reports, on December 5, a special breast cancer patient appeared in Shandong. Saying “special”, one is because the patient is young, only three years old, and the other is because the type of breast cancer is rare, it belongs to secretory carcinoma (SC), and there are only three cases in the world.
News pictures (Source: Sohu)
Actually, these reports are suspected of “title party”, the so-called “third case in the world” “It’s not that there have been three cases of secretory breast cancer in the world, but the disease was diagnosed at the age of three. This is the third discovery.
Like most cancers, breast cancer is inseparable from genetic damage; relatively speaking, middle-aged and elderly people have more “older” genes and experience more trauma. Therefore, breast cancer often occurs in women between the ages of 45 and 55. [2]
In 1966, foreign scholar McDivitt reported a very young breast cancer case. [3] Inside the patient’s tumor cells, there are a large number of vesicles of different sizes; the tumor cells are connected to each other in a spongy shape, forming many tiny cavities. Both vesicles and lacunae imply secretions so rich that some patients produce milk, which is where the name “secretory breast cancer” comes from. [4]
Secretory breast cancer (Source: pathologyoutlines)
Secretory breast cancer was initially discovered in children, most Therefore, the disease was once called juvenile breast cancer. However, subsequent studies have shown that it occurs mostly in adults, with a median age of onset of 25, and accounts for 3 out of 10,000 breast cancers.
At present, it is believed that secretory breast cancer may be a disease related to genetic changes. Fortunately, it rarely metastasizes, and there are not many cases of postoperative recurrence, and the younger the age of onset , the better the prognosis.
hemophilia
On December 4, the State Drug Administration approved a new drug, Emicizumab Injection), for the treatment of hemophilia A (Haemophilia).
To understand hemophilia, you must first understand the body’s blood clotting mechanism. The normal coagulation process can be roughly divided into two steps. The first step is to activate. There are many clotting factors in the blood, which in turn wake up when they encounter a foreign object (such as glass) or when they are exposed to air (blood flowing out of the body). The scouts awakened the front-line generals, and the front-line generals reported the situation to the legion commander, which was passed on and spread continuously. In this process, coagulation factor VIII is the most special. It is not an ordinary messenger, but like a computer, which can accelerate the awakening and increase the speed of the dialogue between coagulation factor IX and coagulation factor X by 200,000 times.
The second step is to deal with it. Thrombin is equivalent to the commander of the legion. After it is awakened, on the one hand, it will directly command the front-line officers and soldiers, stabilize the defense line (generating blood coagulation substances), and on the other hand, call the support of the adjacent corps through the computer (coagulation factor VIII). [5]
It can be seen from this that coagulation factors are an indispensable part of the normal coagulation process. Hemophilia is a genetic disorder in which patients are born with a lack of clotting factors. Once there is trauma, the blood flow will not stop. A deficiency of factor VIII is called hemophilia A, and a deficiency of factor IX is called hemophilia B. Among them, the former is more common, accounting for more than 80% of all hemophilia.
Traditionally, exogenous coagulation factor VIII can be injected into them two to three times a week, so that the coagulation factor VIII in the body reaches a sufficient degree of coagulation. However, some hemophilia A patients (about 1/3) have factor VIII resistance, and even injections are useless.
Emmexel is a synthetic substance, it is like glue that can bind coagulation factor IX and coagulation factor X together, which not only plays the role of coagulation factor VIII, but also does not cause coagulation factor VIII. resistance response. [6]
Mechanism of action of emcydine[6]
multiple sclerosis
In October, “Hellboy” actress Selma Blair admitted that she has Multiple Sclerosis.
Selma Blair (Source: imdb)
Actually, if you pay attention, you will find many Sexual sclerosis-related reports. For example, as the incidence rate rises, major pharmaceutical giants are betting on new drugs for multiple sclerosis; for example, after the recent gene-edited baby incident, some scholars pointed out that the CCR5 gene may affect the survival rate of multiple sclerosis patients.
Multiple sclerosis, not sclerosis, but multiple nerve damage.
Neurons are very similar to trees, with a trunk (axons) and branches (dendrites), and many have a bark (myelin). As the saying goes, trees are afraid of hurting their skin. If the bark is damaged, the nutrients absorbed by the roots cannot be transported upwards, and the tree may die. The myelin sheath is no less important than the bark. First, myelin sheath contains a large amount of lipids, which can provide protection for nerves. Second, myelin sheath can assist in nerve signal transmission, which can not only control the direction of transmission, but also speed up the transmission.
The role of myelin[7]
Sometimes, the immune system is abnormal under the stimulation of genetics, infection, etc. , Crazy attack on myelin sheath, making the original smooth myelin sheath look pimple, like hardening, this is multiple sclerosis. Patients may present with various manifestations such as numbness, pain, visual disturbance, and abnormal movement. [7,8]
Multiple sclerosis (source: medicinenet)
Spinal Muscular Atrophy
Early last year, the Pain Challenge Foundation released the “2018 China Rare Disease Survey Report”. The survey shows that among all rare diseases, Spinal muscular atrophy has the largest number of cases.
The distribution of rare diseases in China[9]
Every sport we play, whether it is writing, playing or shopping, is inseparable from Nerve command. The brain sends commands to the spinal cord, and the spinal cord is further relayed to regulate the corresponding contraction or relaxation of the muscles. It is inferred from this that once the motor nerves in the spinal cord degenerate, the patient may experience abnormal movement, muscle weakness, muscle atrophy, and in severe cases, death due to respiratory muscle “strike”.
conduction of motor commands (image source:togetherinsma-hcp)
This is because of the lack of a protein, the SMN protein.
SMN protein is synthesized by SMN gene, SMN gene is divided into two categories, one is SMN1, which belongs to the main force and synthesizes most of the SMN proteins needed by the human body; the other is reserve, SMN2, which is only responsible for About 10% to 15% of SMN protein is synthesized. SMN protein is widely distributed, plays an important role in the release of neurotransmitters and the metabolism of neurons, and is one of the key regulators of neurons. [10]
SMN gene and SMN protein[11]
In patients with spinal cord dystrophin, congenital lack of SMN1 gene, insufficient. However, the SMN2 gene is very similar to the SMN1 gene. Now there are targeted drugs that increase the copy of the SMN2 gene in the patient’s body. With more genes, the protein expression level increases, and the symptoms of muscle atrophy will be relieved.
The rareness of rare diseases is reflected in two aspects: one is the type, more than 7,000 species have been identified in the world; the other is the absolute number, it is estimated that there are about 18 million patients in China,[12] on average In other words, there is one in every building.
The rarity of rare diseases is aimed at doctors, pharmaceutical companies, and the general population. Because of the low incidence, doctors may misdiagnose, and pharmaceutical companies may be unprofitable and reluctant to produce the corresponding drugs. In 2018, the National Health Commission, in conjunction with the Ministry of Science and Technology, the State Food and Drug Administration and other departments, formulated a special list. The list is divided into two columns, one column lists 121 rare diseases, and the other column recommends hospitals with diagnosis and treatment capabilities for each rare disease. The ratio of 121 to 7000 is of course not much, but it is also a valuable improvement.
Rare Disease Catalog and Corresponding Institutions[13]
As an ordinary person, there is not much that can be done——when browsing related news , to properly consult popular science materials and reduce misunderstandings about rare patients, even if it is to do one’s best.
References
[1] Zhang Shuyang, Xu Haopeng, Zhu Chonggong, Mengchun. Current status and future of rare disease research in China [J]. Concord Medical Journal, 2018, 9 (01): 5–9.
[2] Xie Xing, Gou Wenli. Obstetrics and Gynecology [M]. People’s Health Publishing House, 2013.
[3] MCDIVITT RW, STEWART F W. Breast carcinoma in children[J]. JAMA, 1966, 195(5): 388–390.
[4] Ding Huaye, Gao Lanxiang. Special types of breast cancer[J]. Diagnosis of diseases Journal of Science, 2000, 7(1): 6–9.
[5] Zhu Danian, Wang Tinghuai. Physiology[M]. People’s Health Publishing House, 2013.
[6] OLDENBURG J, MAHLANGU JN, KIM B et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors[J]. New England Journal of Medicine, 2017, 377(9): 809–818.
[7] What is Multiple Sclerosis[R]. MS Society, 2016.
[8] Lv Faxie, Li Zhenxin, Zhang Hua et al. Expert consensus on the diagnosis and treatment of multiple sclerosis and related central nervous system demyelinating diseases in China ( Draft)[J]. Chinese Journal of Neurology, 2006, 12: 025.
[9] 2018 Rare Disease Research Report[R]. Pain Challenge Foundation, Hong Kong Baptist University, Huazhong University of Science and Technology, 2018.
[10] BOWERMAN M, BECKER CG, YÁÑEZ-MUÑOZ RJ et al. Therapeutic strategies for spinal muscular atrophy: SMN and beyond[J]. Disease Models & chanisms, 2017, 10(8): 943–954.
[11] BURGHES AHM, BEATTIE C E. Spinal Muscular Atrophy: Why do low levels of SMN make motor neurons sick?[J]. Nature rev iews. Neuroscience, 2009, 10(8): 597–609.
[12] Intellectuals-Huxiu. There are more than 10 million rare disease patients in China, and the predicament is still [EB/OL]. Huxiu Net, [2018-12-17]. https://www.huxiu.com/article/246838.html.
[13] The list of recommended hospitals for rare diseases is released [EB/OL]. [2018 -12-21].
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